Using double isotope dilution derivative methods specific for digitoxin, digoxin, digitoxigenin, digoxigenin, and the 3-epigenins, the absorption, excretion, biotransformation, distribution, and persistence of digitoxin and digoxin will be studied in man. Digitoxosides and conjugates of the genins and 3-epigenins in excreta and plasma will be determined by hydrolysis of these compounds and measurement of the free genins. Particular attention will be focused on the effect produced on the pharmacodynamics of digitoxin by impaired renal function, hepatic dysfunction, and the administration of drugs that induce microsomal enzymes, such as phenobarbital and diphenylhydantoin. A mole for mole account of the fate of digoxin in human subjects without renal or hepatic disease will be sought.